: The long term goal is to examine and characterize aspects of the working hypothesis that the cerebral cortex and related structures form a neural network mediating learning and memory. Therefore, this project examines changes in representation patterns occurring in the frontal lobe while humans learn motor skills. Functional MRI will measure relative parenchymal perfusion while humans learn to associate arbitrary visual cues with finger movements and during the learning of motor sequences. The first experiment tests the hypothesis that learning changes representation patterns and activates a distinctive network in the frontal lobe. Two different motor skills are examined to assess whether frontal motor areas of humans have separable functions regarding motor skill learning. We expect to observe increases in MR signal intensity and unique activation patterns in several frontal cortical regions during learning. The cortical areas include the precentral gyrus, mesial and lateral portions of the frontal gyrus corresponding to the primary motor cortex and major regions of non primary motor cortex. These data should confirm the existence of multiple cortical areas activated during simple motor actions and should provide evidence for functional segregation of learning simple motor associations. The second experiment tests the hypothesis that slowing the rate of learning and imposing memory requirements on learning elicit activity changes in prefrontal cortex, a target of temporal lobe structures that when disconnected from the frontal lobe impair the rate of learning, a structure thought key to working memory, and a region with connections to motor cortex. A corollary of this hypothesis is that slowing of learning will have no effect on representations in primary motor cortex and non primary motor areas of the frontal gyrus. Learning rate will be changed by either increasing task difficulty or by distraction. The experiments will demonstrate the extent to which neural representations within the cerebral cortex modify during the learning of conditional visual motor associations and motor sequences. Application of the experimental results should enable evaluation of changes occurring in cerebral cortical physiology in human aging, development, neurologic dysfunction, and psychiatric diseases. Understanding the cerebral cortical basis of visual motor associations and sequence learning should enhance rehabilitative strategies for patients with focal brain injury and neurodegenerative and psychiatric diseases.